title: N-Acetyl-S-(1-carbamoyl-2-hydroxy-ethyl)-L-cysteine (iso-GAMA) a further product of human metabolism of acrylamide: comparison with the simultaneously excreted other mercaptuic acids.
abstract: The N-acetyl-S-(1-carbamoyl-2-hydroxy-ethyl)-L: -cysteine (iso-GAMA) could be identified as a further human metabolite of acrylamide. In this study, we report the excretion of d(3)-iso-GAMA in human urine after single oral administration of deuterium labelled acrylamide (d(3)-AA). One healthy male volunteer ingested a dose of about 1 mg d(3)-AA which is equivalent to a dose of 13 microg/kg bodyweight. Over a period of 46 h the urine was collected and the d(3)-iso-GAMA levels analysed by LC-ESI-MS/MS. The excretion of iso-GAMA begins five hours after application. It rises to a maximum concentration (c (max)) of 43 microg/l which was quantified in the urine excreted after 22 h (t (max)). The excretion pattern is parallel to that of the major oxidative metabolite N-acetyl-S-(2-carbamoyl-2-hydroxy-ethyl)-L-cysteine (GAMA). Total recovery of iso-GAMA was about 1% of the applied dose. Together with N-acetyl-S-(2-carbamoylethyl)-L: -cysteine (AAMA) and GAMA, 57% of the applied dose is eliminated as mercapturic acids. The elimination kinetics of the three mercapturic acids of AA are compared. We show that dietary doses of acrylamide (AA) cause an overload of detoxification via AAMA and lead to the formation of carcinogenic glycidamide (GA) in the human body.
authors.affiliation: Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, University of Erlangen-Nuremberg, Erlangen, Germany. eva.hartmann@ipasum.imed.uni-erlangen.de
authors.forename: Eva C
authors.initials: EC
authors.lastname: Hartmann
authors.forename: Melanie I
authors.initials: MI
authors.lastname: Boettcher
authors.forename: Hermann M
authors.initials: HM
authors.lastname: Bolt
authors.forename: Hans
authors.initials: H
authors.lastname: Drexler
authors.forename: Jürgen
authors.initials: J
authors.lastname: Angerer
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism* / Q000652:urine*; D020106:Acrylamide / Q000378:metabolism* / Q000652:urine*; D002273:Carcinogens / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives / Q000378:metabolism*; D004852:Epoxy Compounds / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008297:Male; D015394:Molecular Structure; D010084:Oxidation-Reduction; D012680:Sensitivity and Specificity
chemical_list: D002273:Carcinogens; D004852:Epoxy Compounds; C543946:N-acetyl-S-(1-carbamoyl-2-hydroxy-ethyl)-L-cysteine; D020106:Acrylamide; C071834:glycidamide; D003545:Cysteine; D000111:Acetylcysteine